We will study the thermodynamics and kinetics of (1) the assembly and (2) the fusion of lipoproteins and (3) the exchange of the various components of lipoproteins and model membranes. We will use equilibrium dialysis and microcalorimetry to obtain thermodynamic descriptions of these systems; the kinetics of these three processes will be studies by stopped-flow fluorescence methods. The thermodynamic and kinetic measurements will be conducted on similar systems so that we can take best advantage of the complementary relationship between these two approaches in providing a total physicochemical description of these systems and their interactions. Our aim will be to identify those structural features of the lipids and proteins which are important in regulating lipoprotein formation, exchange and fusion. The components of the systems will be the pure and mixed apolipoproteins and/or model polypeptides with a variety of pure and mixed lipid-protein systems. The apolipoproteins will be those derived from the human plasma high and very low density lipoproteins and the "arginine rich" protein isolated from the plasma of cholesterol fed rabbits. The polypeptides will be those of natural and synthetic fragments of the apolipoproteins and model peptides designed to isolate those structural features in the native proteins which are a prerequisite for binding lipids. The lipid components of these experiments will be various phosphatidylcholines, sphingomyelins and mixtures thereof with and without added cholesterol and cholesteryl esters. Other studies will look at the interaction of the model lipid:protein vesicles with native lipoproteins; these studies will then be extended to the dynamics of the interactions between native lipoproteins. Temperature studies should reveal the relative importance of thermal phase transitions and phase separation of lipids in regulating these processes. The results and implications of these studies will provide a molecular framework for the rational assessment of importance of the composition and structure of lipoproteins and membranes in the development and possible regression of atherosclerosis.